Discovery of Strecker-type α-aminonitriles as a new class of human carbonic anhydrase inhibitors using differential scanning fluorimetry

Figures & data

Figure 1. Melting thermal shift of bovine CA produced by acetazolamide (AZ), a known CA inhibitor (shown in fluorescence/T, °C (left) or derivative fluorescence/T, °C (right) coordinates).

Figure 2. Structures of three Strecker-type α-aminonitriles (1–3) identified as CA T_m shifters in this study.

Figure 3. Melting thermal shift of bovine CA produced by compounds 1 (a), 2 (b), 3 (c) in comparison with that of acetazolamide.

Table 1. Inhibition profile of compounds 1–3 against hCA I, II, IX and XII (h = human).

	Ki, μM*
Compound	hCA I	hCA II	hCA IX	hCA XII
1	0.95	8.51	0.67	5.18
2	3.55	9.20	6.27	7.32
3	6.61	8.11	0.94	7.91
AZ	0.25	0.012	0.025	0.006

*From three different assays, errors ± 10% of the reported value.

Figure 4. Melting thermal shifts of bovine CA produced by various concentrations of KCN in comparison with that produced by AZ.

Figure 5. Melting thermal shifts of bovine CA produced by compounds 1 and 2 (40 μM) with or without addition of vitamin B₁₂.

Scheme 1. Hypothetical mechanism of inhibitory action of Strecker-type α-aminonitriles toward CA.